Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT00634140 |
| Other study ID # |
0710-24 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
March 3, 2008 |
| Last updated |
March 27, 2015 |
| Start date |
August 2009 |
| Est. completion date |
August 2009 |
Study information
| Verified date |
March 2015 |
| Source |
Indiana University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
Ezetimibe is a drug which inhibits the absorption of both dietary and biliary cholesterol in
the small intestine. Ezetimibe has been approved for use in humans to lower serum
cholesterol.
The primary aim of this study is to determine if ezetimibe normalizes resting and residual
volume in patients with chronic acalculous cholecystitis.
Description:
Gallbladder disease continues to be a major healthcare problem in the United States with
more than 750,000 cholecystectomies being performed each year. In the last decade, the
proportion of elective cholecystectomies performed for chronic acalculous cholecystitis has
more than doubled. During this same time, obesity has reached epidemic proportions. In
addition, obesity-induced visceral steatosis is known to cause a local inflammatory process
resulting in organ dysfunction, with nonalcoholic steatohepatitis being a well established
example of this phenomenon. Previous data from our lab also have shown that both congenital
and diet-induced obesity result in cholecystosteatosis, an increase in gallbladder wall fats
accompanied by altered gallbladder motility and absorption. This phenomenon also has been
documented in humans, with patients with chronic acalculous and/or calculous cholecystitis
having increased gallbladder fat than nondiseased controls.
Ezetimibe is a drug which inhibits the absorption of both dietary and biliary cholesterol in
the small intestine. Ezetimibe has been approved for use in humans to lower serum
cholesterol. Moreover, ezetimibe has been shown to ameliorate hepatic steatosis and
cholesterol gallstone formation in animal models. Previous data from our lab have documented
that ezetimibe lowers serum cholesterol, prevents biliary crystals and ameliorates
cholecystosteatosis in lean mice fed a high fat diet. However, the influence of ezetimibe on
gallbladder motility, absorption and accumulation of toxic fats, metabolites, cytokines and
chemokines, cholecystosteatosis, have not been studied in humans. Therefore, the aims of
this study are 1) to determine if ezetimibe normalizes resting and residual volume in
patients with chronic acalculous cholecystitis, 2) to determine if ezetimibe normalizes
gallbladder ion flux in patients with chronic acalculous cholecystitis and 3) to determine
if ezetimibe normalizes gallbladder absorption/secretion modulators as well as gallbladder
fat, cytokines and chemkines.
Subjects with typical biliary pain and or ejection fraction less than 30% on a HIDA scan
will be identified. Patients will then be randomized with one group given ezetimibe and the
other group given placebo. All subjects will have gallbladder ultrasound studies to
determine volume before and after a standardized fatty meal both before starting ezetimibe
or placebo and after 4 weeks. A cholecystectomy will then be performed. In addition, pieces
of the gallbladder taken at cholecystectomy will be analyzed for ion flux, as well as
absorption/secretion modulators and accumulation of toxic fats, metabolites, cytokines and
chemokines.
